The first three years of this grant (1/1/85 - 12/31/87) were a controlled study of nortriptyline for major depressive disorder (MDD) in 6-12 year olds. The next five years (1/1/88 -12/31/92) were a prospective, blindly rated, longitudinal study of the NT drug protocol subjects and two control groups (a newly recruited group of 6-12 year old MDDs and an age, gender, and socioeconomic status matched normal control group). This proposal requests funding to extend the Follow-Up Study for another five years (1 /1 /93-12/31/97). The study population would include 106 subjects (75 MDDs, 31 normals) with a mean age of 15 years old in 1993 increasing to 19 years old by 1997. Every four month assessments of psychiatric, substance use, psychosocial and family history measures would continue to be obtained from participants and second informants. Three times a year data collections would optimize the ability to capture bipolar episodes; investigate state-trait psychosocial factors; identify precipitants of suicidality; and study the effects of comorbidities (dysthymia, conduct, anxiety, substance and eating disorders) on outcome. Further, the effect of TCAs given to 6-12 year old MDDs with familial bipolarity on the development of later hypomanic and manic episodes; frequency of MDD recurrences; and development of rapid cycling would be investigated. Feasibility of intensive data collection from all participants and second informants every four months was demonstrated by the completion rates during the past five years. Of the 110 subjects enrolled, 106 continue to participate which equates to 96.4% retention. There was no interruption in data collection when the PI moved to Washington University from the University of South Carolina on 7/1/91. The same personnel have continued to work on the project since its inception. Because of the increasing body of literature that supports the morbidity and mortality of childhood onset MDD, rigorous naturalistic longitudinal studies are crucial to optimize the design of future prevention and intervention strategies.